Rates of preterm birth in the U.S. have increased in recent years for reasons that remain uncertain. The recent escalation in preterm births in Puerto Rico is especially alarming, where rates since 1997 have gone from just above the U.S. average (12%) to nearly 20% in 2005. While known risk factors for preterm birth have failed to account for this increase, there is mounting evidence that environmental factors may play a key role. This proposed project (Project 3) will utilize state-of-the-art molecular epidemiological methods to explore environmental, genetic, demographic, and behavioral factors that contribute to preterm birth risk in Puerto Rico, and to provide much needed information on the potential mechanistic pathways involved in preterm birth as it relates to environmental factors. Phthalates were chosen as the primary pollutant of interest because they are common contaminants of Superfund sites in Puerto Rico and elsewhere, and recent studies show widespread exposure to phthalates in the U.S. population. Human exposure to some phthalates have increased in recent years, a trend which coincides with the increased rate of preterm birth. Phthalates are classified as emerging pollutants of concern to the SBRP and are associated with reduced gestational age and other effects potentially linked with preterm birth, including inflammation, endocrine disruption, and oxidative stress. Utilizing data and samples generated by recruitment efforts of the Human Subjects core, we will measure urinary phthalate metabolites in 1200 pregnant women. Phthalate metabolite levels will be assessed for associations with residence, water sources, activities, and product use to identify influences of high exposure and opportunities for exposure reduction strategies. Phthalate metabolites will then be used to test associations with declined gestational age and increased risk of preterm birth, as well as with markers of inflammation, endocrine disruption, and oxidative stress to provide data on biologic pathways involved in the association between environmental exposures and early parturition. Analysis of polymorphic alleles in candidate genes will also be conducted among the women for exploration of gene-environment and gene-gene interactions, and to further characterize hypothesized phenotypic markers of individual susceptibility to phthalate exposure based on metabolite ratios. The proposed study will provide much needed information on preterm birth risk factors in Puerto Rico and a rich resource for future investigations.